A research group from CSIC, in collaboration with two other Spanish research groups, has patented a vaccine carrying the gene for the LACK antigen from Leishmania infantum. The vaccine has been tested in mouse and dog, giving good protection results. Othe

Leishmaniasis is a disease caused by intracellular protozoan parasites belonging to the genus Leishmania, belonging to the Trypanosomatide family. The visceral form of the disease, fatal and without treatment, is an endemic disease affecting over 15 million people worldwide, with an estimated incidence of 2 million cases/year, broadly distributed in 88 countries located in tropical and temperate areas (90% in developing countries). It is also endemic in Europe, where its incidence has importantly increased in the last years as it appears as an opportunistic disease associated to AIDS and to other immunodepressed diseases. In countries of the Mediterranean basin, the domestic dog is the reservoir of the disease, with 10% to up to 34% of dogs infected, and is the responsible of the transmission of the disease to humans. In Spain there are around 7 millions dogs, and nearly half of them are domestic dogs.

The Molecular Parasitology group of the Centro de Investigaciones Biológicas from CSIC has developed in the last years a vaccine carrying the gene for the LACK antigen from Leishmania infantum (it is an analogue of the receptor for activated C Kinase). A plasmid containing the LACK gene has been constructed and has been used in several assays using Balb/c mice. Results trying different conditions showed that a prime-boost immunisation regime with DNA plasmid and recombinant vaccinia virus, both expressing the LACK antigen, induces the best protection in mouse.

Nevertheless, the study of the effectivity of the vaccine in the dog was necessary for two reasons. On the one hand, the disease in the dog reproduces many features of the human disease. On the other it is, as indicated, the main host of Leishmania in the Mediterranean basin, including the South of Europe, Asia and America.

The experiments carried out with dogs in collaboration with the Veterinarian Faculty of the Universidad de Zaragoza showed that the protocol prime-boost (1^st dose plasmid-LACK, 2^nd dose vaccinia-LACK) induced protection in at least 60% of the vaccinated dogs. Conditions used to analyse this protection were very restrictive, as researchers considered a dog was protected when it had no clinical signs, but also when the parasite was not present in the animal vaccinated and infected with an inoculation which is one million times higher than the regular dose acquired during the natural infection. Results suggest a Th1 type T-cell mediated immune response in dog, but of different form of that of the mouse. Whereas in mouse is an all-or-nothing immune response, in the dog there is an initial Th1 and Th2 activation, followed by a Th1 response in the immunised animals and a Th2 response in the sick animals. Three different protection experiments were done, with a total of 56 dogs (Beagle dogs), leading to the protection of at least 63% of the dogs.

Complementary studies like the comparison between the activity of the particulated form of the LACK antigen and of the gene in a recombinant vehicle were also carried out. A relevant study was the protection leaded by the recombinant gene, without the following booster of the vaccinia-LACK virus, by intranasal route.  The immunisation results were very satisfactory in the murine model, and there is an experiment on going in dogs. The fact to use only the plasmid and an intranasal administration are important advantages to consider for a vaccine of this nature.

The vaccine has been patented in 2001. The European patent is already granted and the US patent is still not granted.

 

Patents application number 200100402 and 200102057 (addition). European patent (EP 1 371 375) granted. US patent still not granted.

Technical cooperation ; Commercial agreement with technical assistance , License agreement